We intend to carry out a multidisciplinary study of Epidemic Kaposi's Sarcoma (EKS) and associated diseases (AIDS). We shall determine the exact nature of the genetic factors that predispose to these diseases and will attempt to define the nature of the associated immunological disturbances incorporating both autoimmune features and immunosuppression. The immunoglobulin classes involved in the hypergammaglobulinemia and in the circulating immune complexes will be quantitatively defined and the autoantibodies reactive to seminal fluid proteins, sperm and T-cell antigens will be similarly analyzed, as will be the molecular nature of the corresponding antigens. The alterations of cellular immunity will be further characterized with particular reference to the role of the monocyte-macrophage series. The presence of viruses, especially CMV and EBV , will be studied at the DNA and antigen levels, as will be the humoral and cellular aspects of specific immunity against them. Secondary aspects of antiviral defenses, especially the spontaneous and induced production of interferons will also be characterized. We shall also attempt to establish a murine experimental model for AIDS, by eliciting autoimmunity with cellular elements in semen. Innovative approaches to treatment will be initiated using both new modalities of chemotherapy and immunomodulation techniques. Studies on the biology of the KS tumor will also be initiated with the establishment of cultured and transplanted (in athymic nude mice) cell lines. These studies are part of attempts to define the tumor/host relationship which appears to include the production of tumor-promoting humoral factors. A major emphasis will be placed on prospective studies with a large group of currently healthy homosexual men. The presence of autoimmunity, cellular immunodeficiency and exposure to the diverse factors possible contributing to risk will be established in them during a 5-year follow-up with systematic periodic clinical examination. We postulate that it is the interaction between these multiple factors rather than a single agent which cause AIDS and EKS.